5-BROMO-2-ETHOXY-PYRIMIDINE

A stirred solution of 125F Diastereomer mixture (70 mg, 0.210 mmol), 46B. methyl 3-(4-bromo-3-((2-ethoxypyrimidin-5-yl) amino) phenyl) pentanoate (Absolute Stereochemistry not Determined) To a stirred solution of 46A Enantiomer 1 (2 g, 6.98 mmol), A mixture of Example 525A (325.0 mg, 1.601 mmol), bis(pinacolato)diboron (813 mg, 3.20 mmol), potassium acetate (471 mg, 4.80 mmol), and [Iota , - bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane(PdCl2(dppf)-CH2Cl2, 52.3 mg, 0.064 mmol) in dioxane (12 mL) was degassed and heated to 100 C overnight. The solvent was evaporated. The residue was treated with brine and extracted with ethyl acetate (2x). The combined organic layers were dried over MgSO/t, filtered, and concentrated. The residue was purified on a 40 g column using the Biotage Isolera One flash system eluting with heptanes/ethyl acetate (4:6 to 5:5) to provide the title compound (0.343 g, 86%). MS (ESI+) m/z 251.3 (M+H)+.To the solution containing the boronic ester intermediate 2-(2-chlorophenyl)-N-[3- {[(dimethylamino)methylidene]sulfamoyl}-4-(4, 4, 5, 5-tetramethyl-1 , 3, 2-dioxaborolan-2-yl)phenyl]acetamide (100 mg, 198 pmol), To a degassed solution of 153G (0.075 g, 0.199 mmol), To the mixture of 939F Enantiomer 1 (30 mg, 0.07 mmol), 5-bromo-2-ethoxypyridine (21.5 mg, 0.106 mmol), Xantphos (8.2 mg, 0.014 mmol), cesium carbonate (69.2 mg, 0.212 mmol) in 1, 4-dioxane (5 mL), argon gas was bubbled for 5 minutes. Then the bis(dibenzylideneacetone)palladium (4.07 mg, 7.08 mumol) was added and the argon gas was bubbled through the mixture for 5 minutes. The reaction mixture was sealed and heated in sealed tube at 110 C. for 6 h. The reaction mixture was allowed to cool to room temperature and concentrated under reduced pressure to afford the residue. The residue was reconstituted in a mixture of ethyl acetate (20 mL) and water (20 mL). The organic layers were separated and the aqueous layers were extracted with ethyl acetate (2*20 mL). The combined organic layers were washed with water (20 mL), brine (20 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to afford crude 939G Enantiomer 1, taken to next step without further purification (light brown solid, 35 mg, 0.017 mmol, 23.55% yield). LC-MS Anal. Calc'd. for C23H43N5O3, 545.337. found [M+H] 546.4, Tr=3.073 min (Method U).

Molecular Weight:203.04
XLogP3:1.6
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:201.97418
Monoisotopic Mass:201.97418
Topological Polar Surface Area:35
Heavy Atom Count:10
Complexity:93.7
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes